The European Union’s Good Manufacturing Practice (GMP) standards, as outlined in the Annex to the Guide to Good Manufacturing Practice for Medicinal Products, ensure the quality and safety of medicinal products, including those used in clinical trials. The Qualified Person (QP) plays a crucial role in batch certification, particularly for investigational medicinal products (IMPs) used in clinical trials, and how EU GMP standards are upheld through their oversight.

The Role of the Qualified Person in Batch Certification 

The Quality Assurance (QA) is a crucial component of the EU GMP system as defined in Directives 75/319/EEC and 81/851/EEC, ensuring that each batch of medicinal products, including IMPs, meets the necessary legal requirements, including marketing authorization and GMP standards, thereby guaranteeing their safety, effectiveness, and suitability for their intended use.

This Annex signifies that batch certification is mandatory for all finished product batches within the European Community or EEA, including local, imported, and export batches. This requirement extends to IMPs, with specific guidance provided in Annex 13 of the GMP Guide, tailored to their unique considerations.

Significant Responsibilities of the QP

The QP’s routine duties, as outlined in Section 8 of the Annex, are comprehensive and include:

• Adherence and authorization: QP ensures that the batch and its production process align with the standards of the marketing and clinical trial authorization.
• GMP compliance: Making ensure or verify that manufacturing process compiles to EU GMP norms or, for imported products as per the local country standards.
• Process Validation: QP confirms that the principal manufacturing and testing processes are validated and that actual production conditions are considered.
• Deviation Management: Authorizing any deviations or planned changes through a defined system, ensuring regulatory notifications where necessary.
• Testing and Documentation: Ensuring all required checks, tests, and documentation are completed and endorsed by authorized personnel.
• Audits and Inspections: Verifying that all necessary quality assurance audits and inspections have been conducted.

Their responsibilities as QP in IMPs must balance the flexibility of early-phase clinical trials with the stringent quality requirements of GMP.

Batch Certification in Clinical Trials

The QP addresses the complexities of clinical trials, including IMPs produced in smaller batches, multiple manufacturing sites, and evolving protocols, providing guidance on managing batch certification in such scenarios.

Multi-Site Manufacturing and QP Oversight

IMPs may undergo different stages of production, testing, or assembly at various sites, potentially across different countries, and QPs can coordinate certification in these cases:

• Single-Site Manufacturing involves all stages occurring at one site, with the QP certifying the batch either personally or relying on confirmations from other QPs.
• Multi-Site Manufacturing: When stages are split across sites within the same company or different companies, the QP certifying the finished product batch may rely on confirmations from other QPs responsible for intermediate stages
• Bulk and Finished Product Batches: When a bulk production batch is divided into multiple finished product batches, a single Quality Control Point (QP) from the bulk manufacturer coordinates quality issues, ensuring traceability and effective recall if necessary.

These arrangements are especially relevant for clinical trials, where IMPs can be produced in bulk and packaged or labeled at different sites to meet trial-specific requirements.

Challenges and Considerations for IMPs

• Small Batch Sizes: IMPs are often produced in limited quantities, requiring flexible manufacturing processes that still comply with GMP.
• Evolving Formulations: Early-phase trials may involve changes to formulations or processes, necessitating robust deviation management by the QP.
• Global Supply Chains: IMPs are frequently sourced from third countries, complicating oversight and requiring careful coordination between QPs and importers.

Ensuring Traceability and Recall Readiness

A key objective of QP oversight is to ensure that batches can be traced and recalled if a quality issue arises:

• Audit Trails: Documented links between bulk and finished product batch numbers ensure traceability, critical for IMPs distributed across multiple trial sites.
• Written Agreements: These define responsibilities and communication protocols, ensuring that any quality issues are promptly reported to the relevant QP for action.
• Record Keeping: QPs must maintain records of certifications, confirmations, and quality issues to facilitate investigations or recalls.

For clinical trials, this traceability is vital to protect trial participants and maintain the integrity of trial data.

The QP’s Ongoing Professional Development

It is crucial for QPs to maintain up-to-date knowledge of technical and scientific advancements. This is particularly relevant for clinical trials, where new therapeutic modalities (e.g., biologics, gene therapies) may require QPs to acquire specialized expertise. If a QP is tasked with certifying a new product type, they must gain the necessary knowledge and experience, potentially requiring renewed authorization under national regulations.

How Zenovel Assists in QP Oversight and Batch Certification

Zenovel, a top pharmaceutical regulatory and compliance service provider, is instrumental in ensuring QPs adhere to EU GMP standards in clinical trials. We provide expert guidance and streamlines processes, safeguarding the quality of IMPs and trial participants.

• Regulatory Expertise: Zenovel offers comprehensive support to QPs in navigating EU GMP requirements, including those specific to IMPs, ensuring seamless compliance with clinical trial authorizations.
• Multi-Site Coordination: We aids in creating robust written agreements and documentation for multi-site manufacturing, enabling QPs to rely on confirmations from other sites while maintaining oversight and traceability.
• Importation Support: We assist QPs in verifying transport conditions, managing sampling requirements, and ensuring compliance with MRAs or EC/EEA testing obligations for IMPs sourced from third countries.
• Deviation and Quality Management: Our advanced quality systems assist Quality Assurance Professionals (QPs) in managing deviations, validating processes, and maintaining audit-ready documentation, crucial in the dynamic clinical trial environment.
• Training and Development: We provide customized training programs to keep Quality Assurance Professionals (QPs) updated on technical advancements and GMP regulations, ensuring they are well-equipped to certify innovative therapies like biologics and gene therapie

In general, Zenovel’s technology-driven solutions enable QPs to meet EU GMP standards efficiently, advancing medical research with confidence and compliance in the evolving global supply chains and advanced therapies.

Reference:

Annex to the Guide to Good Manufacturing Practice for Medicinal Products: Certification by a Qualified Person and Batch Release, by EUROPEAN COMMISSION ENTERPRISE DIRECTORATE-GENERAL